Transparent glassy cannabinoid compositions

ABSTRACT

The disclosure provides methods and compositions for providing shatter formulations taking the form of crystalline polymorphs, where methods of preparation include preparing tetrahydrocannabinol acid (THCA) powder followed by decarboxylating THCA and removal of terpenes.

This application claims the benefit of, and priority to U.S. ProvisionalPatent Application Ser. No. 62/556,418 filed Sep. 9, 2017, and is acontinuation of, and claims priority to, U.S. patent application Ser.No. 16/127,150 filed Sep. 10, 2018, the contents of both of which areincorporated herein by reference herein in their entirety.

BACKGROUND OF THE SYSTEM

The cannabinoids from Genus Species include tetrahydrocannabinolic acid(THCA), cannabidiolic acid (CBDA) and cannabigerolic acid (CBGA),tetrahydrocannabinol (CBD), cannabichromene (CBC), cannabigerol (CBG),delta-9-tetrahydrocannabinol (delta-9-THC), and cannabinol (CBN) (see,US 2015/0152018 of Raber et al and US 2015/0080265 of Elzinga et al,each of which is incorporated herein in their entirety, Appendino et al(2008) J. Nat. Prod. 71:1427-1430). Regarding delta-8-THC, an origin ofdelta-8-tetrahydrocannabinol (delta-8-THC) is described (Owens et al(1981) Clin. Chem. 27:619-624). The present disclosure provides newformulations and products comprising cannabinoids and terpenes, canencompass unique crystalline polymorphs, and where the products madefrom the formulations can have a consistency ranging from brittle totaffy-like.

SUMMARY

Briefly stated, the present disclosure provides a mortar and pestlemethod that provides a formulation from an amorphous THCA powder. Alsoprovided are compositions made by that method. Also provided is a DACmethod that provides a formulation from an amorphous THCA powder.Compositions made by that method are also provided. In addition, aremethods that provide formulations from a crystalline THCA powder. Whatis provided is a solution-phase, pre-formulation that provides aformulation form a crystalline THCA powder. Compositions made from thismethod are also provided. Moreover, what is provided is solid phasepre-formulation and syringe pump method that provides formulation fromcrystallizing THCA powder. Compositions from this method are alsoprovided.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 . Flow chart with steps including extraction, winterization,filtering, and decarboxylation.

DETAILED DESCRIPTION OF THE SYSTEM

As used herein, including the appended claims, the singular forms ofwords such as “a,” “an,” and “the” include their corresponding pluralreferences unless the context clearly dictates otherwise. All referencescited herein are incorporated by reference to the same extent as if eachindividual patent, and published patent application, as well as figures,drawings, sequence listings, compact discs, and the like, wasspecifically and individually indicated to be incorporated by reference.

Identifying Polymorphs

Compositions of the present disclosure, including polymorphs, can becharacterized by Differential Scanning calorimetry (DSC), FourierTransform Infrared Spectroscopy (FTIR), Fourier Transform Near-InfraredSpectroscopy (NIR), Powder X-Ray Diffraction (PXRD), Thermal GravimetricAnalysis (TGA), Solid State Nuclear Magnetic Resonance (SSNMR).Additional methods include atomic absorption spectroscopy, titrimetricassays, raman spectra, and ion chromatography.

U.S. Pat. No. 7,091,246, which is incorporated, herein in its entirety,provides the following account of how scanning calorimetry is used.Differential Scanning calorimetry (DSC) measures heat now as a functionof time or temperature and is used to study material transformationwhether they be physical, such as phase changes, or chemical, such asdecomposition. Parameters that can he obtained from a DSC thermograminclude, onset temperature, the temperature of the peak minimum, and thepeak width. DSC provides information on purity. For example, when a purecrystalline substance melts, the melting point is sharp. In DSC, thatsharpness is shown by a narrow melting peak in the thermogram. If thereare impurities or defects in the crystalline nature, the melting takesplace at lower temperatures and over a larger range of temperatures. InDSC, the impurities are shown by a lower onset temperature and peaktemperature, and a broader peak in the thermogram. When there arediscrete impurities, they can melt at their melting points. In DSC,discrete impurities can be shown by additional peaks in the thermogram.Decomposition may be a parameter of interest, when characterizingpolymorphs. While a decomposition curve is usually broader and can bemore complicated, some of the same phenomena are seen as with melting.Impurities and defects will cause broader and lower temperature peaks.Discrete impurities can show their own decomposition peaks.

A solid material that can exist as two or more polymorphs can becharacterized according to whether it is enantiotropic or monotropic.Solid phase transitions that transform reversibly without passingthrough the liquid or gas phase are enantiotropic transitions. But wherethe polymorphs are not convertible without passing through liquid or gasphase, the system is monotropic and the transition, when it occurs, is amonotropic transition (see, Carletta et al (2015) Solid-stateinvestigation of polymorphism and tautomerism of phenylthiazole-thione;a combined crystallographic, calorimetric and theoretical survey. Cryst.Growth Des. 15:2461-2473).

The present disclosure encompasses methods for creating differentpolymorphic forms, or for creating different ratios of variouspolymorphic forms. These methods include solvent effects, for example,where the packing of a crystal can differ in polar versus in nonpolarsolvents. These methods include adding an impurity that inhibit growthpatterns and favors the growth of a metastable polymorph. Anothermethod, is altering the level of supersaturation from which material iscrystallized (the higher the concentration above the solubility, themore likely is metastable formation). Other parameters that can bevaried, are temperature used during crystallization, and degree ofstirring.

Cannabinoids

One of more of the following cannabinoids can be included in thecompositions of the present disclosure. Alternatively, one of more ofthe following cannabinoids can be excluded (omitted) from thecompositions and methods of the present disclosure. Cannaboids andrelated compounds include, for example, cannabigerol; cannabichromene;cannabitriol; cannabidiol; cannabicyclolol; cannabielsoin,cannabinodiol; cannabinol; delta-8-tetrahydrocannabinol;delta-9-tetrahydrocannabinol; cannabichromanone; cannabicoumaronone;cannabicitran; 10-oxo-delta-6a10a-tetrahydrocannabinol; cannabiglendol;delta-7-isotetrahydrocannabinol; CBLVA; CBV; CBEVA-B; CBCVA;delta-9-THCVA; CBDVA; CBGVA; divarinolic acid; quercetin; kaemferol;dihydrokaempferol; dihydroquercetin; cannflavin B; isovitexin; apigenin;naringenin; eriodictyol; luteolin; orientin; cytisoside; vitexin;canniprene; 3,4′-dihydroxy-5-methoxy bibenzyl; dihydroresveratrol;3,4′-dihydroxy-5,3dimethoxy-5′-isoprenyl; cannabistilbene 1;cannabistilbene 11a; cannabistilbene 11b; cannithrene 1; cannithrene 2;cannabispirone; iso-cannabispirone; cannabispirenone-A;cannabispirenone-B; cannabispiradienone; alpha-cannabispiranol;beta-cannabispiranol; acetyl-cannabispirol;7-hydroxy-5-methoxyindan-1-spiro-cyclohexane;5-hydroxy-7-methoxyindan-1-spiro cyclohexane; myristic acid, palmiticacid, oleic acid, stearic acid, linoleic acid, linolenic acid, arachidicacid, eicosenoic acid, behenic acid, lignoceric acid,5,7-dihydroxyindan-1-cyclohexane; cannabispiradienone;3,4′-dihydroxy-5-methoxybibenzyl; canniprene; cannabispirone;cannithrene 1; cannithrene 2; alpha-cannabispiranol;acetyl-cannabispirol; vomifoliol; dihydrovomifoliol; beta-ionone;dihydroactinidiolide; palustrine; palustridine; plus-cannabisativine;anhydrocannabisativine; dihydroperiphylline; cannabisin-A; cannabisin-B;cannabisin-C; cannabisin-D; grossamide; cannabisin-E; cannabisin-F;cannabisin-G; and so on (see, e.g., Flores-Sanchez and Verpoorte (2008)Secondary metabolism in cannabis in Phytochem. Rev. DOI10.1007/s11101-008-9094-4). Suppliers of tetrahydrocannabinolic acid(THCA) and other cannabinoids include Sigma-Aldrich, St. Louis, Mo. andEcho Pharmaceuticals, Rijnkade 17B, The Netherlands.

Measuring Cannabinoids

Cannabinoids can be separated, purified, analyzed, acid quantified by anumber of techniques. Available equipment and methods include, gaschromatography, HPLC (high pressure liquid chromatography, highperformance liquid chromatography), mass spectrometry, time-of-flightmass spectrometry, gas chromatography-mass spectrometry (GC-MS), andliquid chromatography-mass spectrometry (LC-MS). Equipment forseparation and analysis is available from Waters Corp., Milford, Mass.;Agilent, Foster City, Calif.; Applied Biosystems, Foster City, Calif.;and Bio-Rad Corp., Hercules, Calif.

The present disclosure provides in-line monitoring, of purification,that is, quantitation THC as well as quantitation of impurities. In-linemonitoring may be by UPLC methods, or by other methods. Ultra-highperformance liquid chromatography (UPLC) is similar to HPLC, except thatUPLC uses smaller particles in the column bed, and greater pressures.The particles can be under 2 micrometers in diameter, and pressures canbe nearly 15,000 psi. UPLC also uses higher flow rates, and can providesuperior resolution and run times in the range of under 30 seconds (Wrenand Tchelitcheff (2006) J. Chromatography A. 1119:140-146; Swartz, M. E.(May 2005) Separation Science Redefined). The application of UPLC tocannabinoids has been described (see, Jamey et al (2008) J. AnalyticalToxicology. 32:349-354; Badawi et al (2009) Clinical Chemistry.55:2004-2018). Suitable UPLC columns for cannabinoid analysis include,e.g., Acquity.®. UPLC HSS T3 C18, and Acquity.®. UPLC BEH C18 column(Waters, Milford, Mass.). Other methods for detecting cannabinoidsinclude, e.g., infrared (IR) spectroscopy, gas chromatography massspectroscopy (GCMS), and electrospray tandem mass spectroscopy(ESI-MS/MS) (Ernst et al (2012) Forensic Sci. Int. 222:216-222).Biochemical properties of terpenes, including receptor binding, can beassessed using labeled terpenes and labeled ligands where a terpeneinfluences binding properties of the labeled ligand. Useful labelsinclude radioactive labels, epitope tags, fluorescent dyes,electron-dense reagents, substrates, or enzymes, e.g., as used inenzyme-linked immunoassays, or fluorenes (see, e.g., Rozinov and Nolan(1998) Chem. Biol. 5:713-728).

Terpenes

The present disclosure provides terpenes, either endogenous or exogenous(intentionally added), as a component of a cannabinoid composition.

Berry GDP (Berry Granddaddy Purple) blend ingredients include thefollowing. The top ten in descending order of prominence are:beta-myrcene, beta-caryophyllene, alpha-pinene, linalool, valencene,alpha-humulene, beta-ocimene, beta-pinene, D-limonene, andalpha-bisabolol. Provided is composition that contains only theseterpenes (consists of only these terpenes). Also, provided is acomposition that comprises these terpenes.

Pineapple Super Silver Haze blend ingredients include the following. Topten components in descending order of prominence: Terpinolene,beta-myrcene, beta-ocimene, D-limonene, beta-caryophyllene, beta-pinene,alpha-pinene, alpha-phellandrene, alpha-humulene, and alpha-terpinene.Provided is composition that contains only these terpenes (consists ofonly these terpenes). Also, provided is a composition that comprisesthese terpenes.

Tropical Trainwreck is a terpene blend that contains these top 10 indescending order of prominence: Terpinolene, beta-caryophyllene,D-limonene, beta-myrcene, beta-pinene, ocimene, alpha-pinene, valencene,alpha-humulene, terpineol. Provided is composition that contains onlythese terpenes (consists of only these terpenes). Also, provided is acomposition that comprises these terpenes.

Some examples of terpenes, and their classification, are as follows:

Hemiterpenes: Examples of hemiterpenes, which do not necessarily have anodor, are 2-methyl-1,3-butadiene, hemialboside, and hymenoside;

Monoterpenes: pinene; alpha-pinene, beta-pinene, cis-pinane,trans-pinane, cis-pinanol, trans-pinanol (Erman and Kane (2008) Chem.Biodivers. 5:910-919), limonene; linalool; myrcene; eucalyptol;alpha-phellandrene; beta-phellandrene; alpha-ocimene; beta-ocimene,cis-ocimene, ocimene, delta-3-carene; fenchol; sabinene, borneol,isoborneol, camphene, camphor, phellandrene, alpha-phellandrene,alpha-terpinene, geraniol, linalool, nerol, menthol, myrcene,terpinolene, alpha-terpinolene, beta-terpinolene, gamma-terpinolene,delta-terpinolene, alpha-terpineol, trans-2-pinanol,

Sesquiterpenes: caryophyllene; beta-caryophyllene, caryophyllene oxide,humulene, alpha-humulene, alpha-bisabolene; beta-bisabolene; santalol;selinene; nerolidol, bisabolol; alpha-cedrene, beta-cedrene,beta-eudesmol, eudesm-7(11)-en-4-ol, selina-3,7(11)-diene, guaiol,valencene, alpha-guaiene, beta-guaiene, delta-guaiene, guaiene,farnesene, alpha-farnesene, beta-farnesene, elemene, alpha-elemene,beta-elemene, gamma-elemene, delta-elemene, germacrene, germacrene A,germacrene B, germacrene C, germacrene D, germacrene E.

Diterpenes: oridonin, Triterpenes: ursolic acid; oleanolic acid; “1.5ene”; guaia-1(10), 11-diene can be characterized as a 1.5 ene.Guaia-1(10),11-diene is halfway between a monoterpene and diterpene, interms of how many isoprenoid units are present. Monoterpene isC.sub.10H.sub.16, and diterpene is C.sub.20H.sub.32. Guaia-1(10),11-diene is C.sub.15H.sub.24. Isoprene is C.sub.5H.sub.8 (two doublebonds).

Terpene formulations of the present disclosure may comprise one or moreselected from a list comprising alpha-bisabolol, borneol, camphene,camphor, beta-caryophyllene, delta-3-carene, caryophyllene oxide,alpha-cedrene, beta-eudesmol, fenchol, geraniol, guaiol, alpha-humulene,isoborneol, limonene, linalool, menthol, myrcene, nerol, cis-ocimene,trans-ocimene, alpha-phellandrene, alpha-pinene, beta-pinene, sabinene,alpha-terpinene, alpha-terpineol, terpinolene, alpha-guaiene, elemene,farnesene, germacrene B, guaia-1(10), 11-diene, trans-2-pinanol,selina-3,7(11)-diene, eudesm-7(11)-en-4-ol, and valencene. See, US2015/0080265 of Elzinga et al, which discloses these and other terpenesand terpene formulations, ranges, terpene combinations, exclusionaryembodiments, suppliers of chemicals, human subject sensory panels, andthe like, all of which are incorporated herein by reference.

Terpenes modify and modulate the effects of THC and other cannabinoidsand impact the overall medicinal properties of the particular cultivar.Physiological effects can be detected when inhaled from ambient air,where the result is serum levels in the single digit mg/mL range (see,US 2015/0080265 of Elzinga and Raber, which is incorporated herein byreference in its entirety). Terpenes display unique therapeutic effectsthat may contribute to the overall effects of medicinal cannabis. Thesynergy of terpenes and cannabinoids are likely responsible forproviding the effective treatment of pain, anxiety, epilepsy,inflammation, depression, and infections (McPartland and Russo (2001) J.Cannabis Ther. 1:103-132).

The term “entourage effect” refers to the influence of the combinationof cannabinoids and terpenes that results in synergic effects onphysiology (Russo (2011) Brit. J. Pharmacol. 163:1344-1364; Corral(2001) J. Cannabis Therapeutics. vol. 1, issue 3-4). Terpenes incannabis have been described. See, Flores-Sanchez and Verpoorte (2008)Phytochem. Rev. 7:615-639, and US2015/0080265 of Elzinga and Raber andUS2015/0152018 of Raber and Elzinga, each of which is incorporatedherein in its entirety.

This describes butane hash oil (BHO). Butane hash oil is a high-potencycannabis concentrate that has much higher THC content than flowercannabis. See, Miller et al (2016) J. Psychoactive Drugs. 48:44-49; Chanet al (2017) Drug Alcohol Depend. 178:32-38; Meier M H (2017) DrugAlcohol Depend. 179:25-31.

Butane hash oil (BHO) is a concentrate or extract derived from plantmaterial, utilizing n-butane or a similar light alkane to perform theextraction process, where the extraction solvent is easily removed,following the extraction procedure. Solvent-based extraction is whereplant matter containing extractable compounds is bathed or washed in asolvent. The extractable compounds from the plant material dissolve inthe solvent. The solution is then purified to remove the solvent andrecover the desired extracted compounds. Optionally, the purificationprocess involves beating the solution to boil off or volatilize thesolvent from the solution, leaving the extracted compounds behind. Suchextraction methods use a solvent having a lower boiling point than theboiling points of the products, and in this way, the solvent can beremoved without removing the extracted compounds with minimizingheat-induced damage to the extracted compounds. U.S. Pat. No. 9,327,210of Jones describes method to prepare butane hash oil (BHO). Process ofextracting hash oil from cannabis plant material often involves runningbutane, a hydrocarbon-based solvent, through the plant material orsoaking the plant material in butane to wash out the cannabinoids. Thecannabinoid-rich solvent solution is then purified, often by heating it,which volatilizes the butane and leaves behind the cannabinoid extract(see, U.S. Pat. No. 9,327,210 of Jones, which is incorporated herein byreference in its entirety). Butane is preferably a food-grade, refinedn-butane or isobutane.

Decarboxylation of THCA

THCA compounds can be decarboxylated. For example, Dussy et al achieveda 70% yield with treatment of a dry THCA compounds at 150 degrees C.(see, Dussy et al (2005) Isolation of Delta-9-THCA-A from hemp andanalytical aspects concerning the determination of Delta9-THC incannabis products. 149:3-10). Drying was with nitrogen gas.Decarboxylation can be, for example, under the condition of 80 degrees,95 degrees C., 110 degrees C., 130 degrees C., 145 degrees C., 150degrees C., 175 degrees C., 200 degrees C., 225 degrees C. and like.Drying can be for various times up to 60 minutes, or up to 90 minutes,or up to 120 minutes, and so on. Drying can be in the dried state undernitrogen gas, or in a dried state under atmospheric air, or as dissolvedin a solvent such as methanol, acetonitrile, or tetrahydroforan, as anemulsion in water, or suspended in a non-ionic detergent in water, orsuspended in an ionic detergent in water.

Wiped Film Evaporation

Wiped film evaporation has been described by one supplier, LCI Corp,Charlotte, N.C. Without implying any limitation on the presentdisclosure, LCI Corp.'s description is, “The agitated thin filmevaporator, commonly referred to as a “wiped film evaporator,” consistsof two major assemblies: a cylindrical heated body and a rotor. Productis introduced above the heated zone and is evenly distributed over theevaporator's inner surface by the rotor. As the product spirals down thewall, the high rotor tip speed generates highly turbulent flow resultingin the formation of bow waves and creating optimum heat flax and masstransfer conditions.

Volatile components are rapidly evaporated via conductive heat transfer.Vapors flow either counter-currently or co-currently through the unit,depending on the application requirements. In both cases, vapors areready for condensing or subsequent processing, that is, fractionation,after exiting the vapor discharge section.

Nonvolatile components are discharged at the outlet. Continuousagitation and mixing by the rotor blades minimizes fouling of thethermal wall where the product or residue is most concentrated. Thecombination of 1) extremely short residence time, 2) narrow residencetime distribution, 3) high turbulence, and 4) rapid surface renewalpermits the thin film evaporator to successfully handle heat-sensitive,viscous and fouling-type fluids.”

A description of wiped film evaporation from another supplier, PopeScientific, Saukville, Wis., reads, “Short Path/Wiped-Film Stills (WFS)and Wiped-Film Evaporators (WFE) successfully separate volatile fromless volatile components for Oils, Fats, Chemicals, Polymers,Nutraceuticals, Fragrances, with a gentle process utilizing thethin-film wiping action of feed liquid through a heated cylindricalvacuum chamber with high vacuum (vacuum distillation/evaporation). Keysto the superiority of this process include: Short residence time of thefeed liquid, Significantly lowered temperature due to high vacuumcapability, and Optimal efficiency in mass and heat transfer. The brief(seconds) exposure of feed liquid to heated walls is due in part to theslotted wiper design which forces the liquid downward with strictcontrol of residence time, film thickness, and flow characteristics.”

Dual Asymmetric Centrifugal Mixing

DAC cup is a high shear mixer used in the THC coating method of saltsand sugars, as applied to the compositions and methods of the presentdisclosure. DAC cup is Dual Asymmetric Centrifugal mixing unit.

One supplier of Dual Asymmetric Centrifuge (FlackTek, Inc. Landrum,S.C.) describes DAC as, “The SpeedMixer DAC 10000 HP works by thespinning of a high speed mixing arm in one direction while the basketrotates in the opposite direction, thus, the name Dual AsymmetricCentrifuge. This combination of forces in different planes enablesincredibly fast mixing, and yet the precision construction of eachmachine gives it a balance that allows amazingly quiet operation.

With this instrument, the typical mixing time for fully dispersing acolour paste in a silicone sealant is less than 10 seconds; for mixingfumed silica or precipitated chalk silicone formulations 8-14 secondswill normally suffice. These are both operations that would otherwiserequire up to 3 hours or more of mixing time, and they can only be donein quantities of 1 quart or greater. Mixing does not incorporate any airand additional mixing time removes air from the blend, yielding afinished product when the mixing process is done. Fluids of widelydiffering viscosities can be blended quickly.

Rheometers for Measuring Consistency of Resin, Taffy-Like Substances,and Liquids

Consistency of the compositions of the present disclosure, in terms ofviscosity of resins and of taffy-like substances, can be measured with arheometer. Torque rheometers are available (see, Brabender Plastigraph,Brabender GmbH, Duisburg, Germany; Haake Rheocord, Thermo Electron Corp.Newington, N.H.). These can take measurements on plastic resins, forexample. Viscosity of substances with a taffy-like consistency, as wellas of waxes and liquids, can be measured with TA Instruments AR2000rheometer (TA Instruments, New Castle, Del.) and Brookfield DVIIIrheometer (Brookfield Engineering Laboratories, Middleboro, Mass.).

Polymorphs of the Present Disclosure

The present disclosure provides polymorphs that arise from usingdifferent salts, that is, one type of salt causing the composition toassume a first polymorph and a second type of salt causing thecomposition to assume a second polymorph. Moreover, the disclosureprovides polymorphs arising from using a different counterion, that is,changing only the anion component of a salt, where the result is eithera first polymorph or a second polymorph. Additionally, what is providedis polymorphs arising from using a different counterion, involvingchanging the cation counterion of the salt, resulting in either a firstpolymorph or, a second polymorph. Polymorphs of the present disclosurecan be produced by solvent effects, intentionally added impurities,level of supersaturation from which material is crystallized,temperature at which crystallization occurs, stirring conditions, and soon, or any combination of the above. Physical properties can define thecompositions of the present disclosure, including inciting point,stability to decarboxylation, and other properties, characteristics, andparameters as disclosed, for example, by Soda (U.S. Pat. No. 9,499,543,Okumura (WO2014/104414), and Rushforth (U.S. Pat. No. 7,091,246). Forexample, melting point of commercially available THCA is 78-88 degreesC.

DETAILED DESCRIPTION OF THE FIGURES

FIG. 1 . This provides a flow chart showing the steps of extraction andwinterization, which are carried out in cold ethylacetate. The veryfirst step in the flow chart is extraction. A preferred solvent isn-butane in this extraction procedure. However, any light hydrocarbon,such as, propane, methylbutane tetrafluoroethane, is expected also towork for purposes of this type of extraction. The winterized product(BHOwinterized) can then be subjected to either 40-50% ACN/filtering orto LithCarb 75-80%. BHO means Butane Hash Oil. LithCarb means lithiumcarbonate (Li.sub.2CO.sub.3). Carbonate is the base used to basify theTHCA to make it soluble in water. Lithium is the counterion that mayhave an additional effect of creating the polymorph/salt. Lithiumcarbonate is critical to this process because it works where othercommonly used carbonate bases, such as sodium carbonate, do not. Alongwith the use of acetonitrile (ACN) as solvent, the use of lithiumcarbonate is a unique and novel step because it enables this process andthe resulting composition of matter. One advantage of LithCarb path iselimination of all known pesticides. Also, the acetonitrile (ACN) stepprovides the advantage of removing some or all pesticides.

Pesticide-free embodiments are provided. The methods, procedures, andcompositons of the present disclosure can be substantiallypesticide-free. This can refer to all pesticides (natural as well assynthetic), naturally occurring pesticides, or synthetic pesticides. Inembodiments, the pesticide level can be in terms of weight in a THCApowder, weight in a raw distillate, weight in a hard, sticky paste, andso on. Also, the pesticide level can be in terms of weight of pesticidein a kilogram of dried plant matter, weight of pesticide in a kilogramof “wet” plant matter is it occurs at the time of being harvested, interms of total pesticides, or in terms of an individual pesticide, or interms of a combination of any two, any three, any four, or any fivepesticides. A number of pesticides are named below.

The pesticide weight can be under 10 picograms (pg)/kg, under 20 pg/kg,under 40 pg/kg, under 60 pg/kg, under 100 pg/kg, under 200 pg/kg, under400 pg/kg, under 800 pg/kg, under 1000 pg/kg, under 10 nanograms(ng)/kg, under 20 ng/kg, under 40 ng/kg, under 60 ng/kg, under 80 ng/kgunder 100 ng/kg, under 200 ng/kg, under 400 ng/kg, under 600 ng/kg,under 800 ng/kg, under 1 micrograms/kg, under 2 micrograms/kg, under 4micrograms/kg, under 6 micrograms/kg, under 8 micrograms/kg, under 10micrograms/kg, under 20 micrograms/kg, under 40 micrograms/kg, under 60micrograms/kg, under 80 micrograms/kg, under 100 micrograms/kg, under0.2 mg/kg, under 0.4 mg/kg, under 0.6 mg/kg, under 0.8 mg/kg, under 1.0mg/kg, under 2 mg/kg, under 4 mg/kg, under 6 mg/kg, under 8 mg/kg, under10 mg/kg, under 20 mg/kg, under 40 mg/kg, under 60 mg/kg, under 80mg/kg, under 100 mg/kg, under 200 mg/kg, under 400 mg/kg, under 600mg/kg, under 800 mg/kg, under 1,000 mg/kg, and so on.

Pesticides include, Aldicarb, Abamectin, Azoxystrobin, Bifenazate,Boscalid, Bifenazate, Bifenthrin, Carbaryl, Cypermetrin, Cyflutrin,Chlofenapyr, Chlorpyrifos, Captan, Dimethomorph, Diazinon, Diaminozide,Etoxazole, Fenhexamide, Fenoxycarb, Fenpyroximate, Flonicamid,Fludooxonil, Hexythiazox, Imidacloprid, Myclobutanil, Malathion,Paclobutrazole (Bonzi), Piperonyl butoxide, Pyrethrins, Propiconazole,Permetrin, Spinosad, Spinetoram, Spirotetramat, Spiromesifen,Tebuconazole, Thiamethoxam, Trifloxystrobin.

Winterization is a cannabinoid purification process in which a crudecannabis extract is subjected to a solvent, typically ethanol, thatdissolves the cannabinoids but causes fats and waxes to precipitate. Thesolid fats and waxes are then separated from the solution of purifiedcannabinoids via filtration.

In the flowchart of FIG. 1 , the steps near the top show the conversionof BHOwinterized to a white THCA powder. In the flow chart, the stepsshown near the bottom also show the conversion of BHOwinterized to whiteTHCA powder. For both the upper series of steps and for the lower seriesof steps, branch points can occur where the composition is subjected todecarboxylation/deterpenization. Deterpenation means removal ofterpenes. The conditions for decarboxylation/deterpenation are,Temperature: 130 degrees C., Pressure: 0.1 Torr, Time: 2 hour.

The lower series of steps shows use of silica plug. A silica “plug” is asmall quantity of silica gel that the solution of THCA in heptane isfiltered through. Silica gel and glass are both composed of silicondioxide. Silica gel differs in that it is silicon dioxide in powder formwith a very small particle size as compared, for example, to sand. Theupper series of steps and the lower series of steps show filtrationsteps. “Filter” denotes the operation of filtration rather than the useof a filter. Multiple types of filters can be used in this process andthe pore size is not critical.

The final step of the flow chart, which are shown at the far left(bottom), and which occurs immediately after thedecarboxylation/deterpenation step, is the wiped film evaporation (WFE)step.

Narrative for the Flow Chart Boxes of FIG. 1

Mother liquor. Mother liquor is shown in flow chart boxes 4, 10, and 11.Mother liquor is the remaining acetonitrile solution of winterized BHO.This solution contains some THCA in it because THCA is sparingly solublein acetonitrile. In these flow chart boxes, the THCA powder is leftsitting on top of the filter, while the mother liquor has passed throughthe filter.

Yields. Yields are shown for various steps, that is, in the transitionfrom a given box to the next box. Yields were determined to be 40-50%(Box 3 to Box 4), 90-95% (Box 4 to Box 5), 75-80% (Box 3 to Box 8),75-80% (Box 8 to Box 9), and 70-80% (Box 9 to Box 10). A relatively lowyield, such as 40-50%, may be due to some of the THCA still dissolved inthe acetonitrile mother liquor, and where only a portion of the THCAprecipitates as a white powder.

Processing pathways. The flow chart boxes of FIG. 1 illustrate variousprocessing pathways, such as that beginning with Box 1 (flower) andending at Box 10 (THCA powder), or beginning with Box 1 (flower),continuing to Box 10 (THCA powder), and continuing throughdecarboxylation/deterpenation step and then wiped film evaporator (WFE)step, and concluding at Box 13 (raw distillate). The dashed line in theflow chart indicates decarboxylation/deterpenation step. As shownimmediately below, the advantages of one or more of the indicated flowchart processing pathways can be the isolation of high purity THCA witha simple solvent extraction, or the production of a product that isclearer and less colored, or the production of a product with a greateryield.

(A) Boxes 1, 2, 3, 4, 5. Advantage: Allows the isolation of high purityTHCA with a simple solvent extraction. Disadvantage: Low yield

(B) Boxes 1, 2, 3, 4, 6, 7. Advantage: Allows the isolation of highpurity THC with a simple solvent extraction followed by decarboxylationand WFE. Disadvantage: same as (A)

(C) Boxes 1, 2, 3, 4, 8, 12, 13. Advantage: Same as (B). Disadvantage:same as (A)

(D) Boxes 1, 2, 3, 4, 8, 11, 12, 13. Advantage: Produces a clearer (i.e.more colorless product) compared to (C). Disadvantage: Lower yield than(C)

(E) Boxes 1, 2, 3, 8, 12, 13. Advantage: Similar to (C) but higher yield

(F) Boxes 1, 2, 3, 8, 11, 12, 13. Advantage: Similar to (D) but higheryield

(G) Boxes 1, 2, 3, 8, 9, 10, 12, 13. Advantage: Similar to (F) butproduces a clearer (i.e. more colorless product) compared to (F)

(H) Boxes 1, 2, 3, 8, 9, 10. Advantage: Similar to 1, 2, 3, 4 [Like epathway in (A)] but higher yielding.

Raw distillate. This concerns “raw distillate.” Anywhere that “rawdistillate” is required in a procedure to make one or more embodimentsof the present disclosure, the products denoted by Block 12 or by Block13 can be used. Raw distillate is not an integral ingredient inProtoshatter of the present disclosure, that is, it is the ease thatsome embodiments of Protoshatter include raw distillate, while otherembodiments do not include raw distillate.

As shown by the flow chart of FIG. 1 , “raw distillate” is the result ofprocedures that include decarboxylation/deterpenization. Applicants haveroutinely conducted quantitative chemical conversion and routinelyreached yields of 100%. Tn embodiments, the present disclosureencompasses compositions and methods, where decarboxyation is at least50%, at least 60%, at least 70%, at least 80%, at least90%, at least95%, at least 99%, and so on. Also, the present disclosure encompassescompositions and methods, where decarboxyation is about 50%, about 60%,about 70%, about 80%, about 90%, about 95%, about 99%, and so on.

THCA powder. THCA powder is a required component is required by all fourof these methods of the present disclosure: (1) Mortar and PestleMethod; (2) DAC Method; (3) Solution-Phase Pre-Formulation; and (4)Solid Phase Pre-formulation and Syringe Pump Method. As shown in theflow chart of FIG. 1 , THCA powder is produce in blocks 4, 5, 9, 10, and11. THCA powder that is produced by the previous steps that terminate inany of these blocks can be used for making Protoshatter. What ispreferred for making Protoshatter, is the THCA powder from blocks 5, 10,and 11, because these THCA powders are colorless (a desired attribute).

EXAMPLES Example 1

Procedures of the present disclosure provided a composition that may bea form of a lithium salt that is not a crystal polymorph or,alternatively, a crystal polymorph. Elemental analysis or 2D NMR maydistinguish between these two possibilities. Also, procedures of thepresent disclosure provided a THCA composition that is different fromcommercially available THCA, where the THCA composition wasdistinguished from commercially available THCA by melting point, andwhere the different melting points indicated two different polymorphs(the present THCA versus commercially available THCA). THCA compositionprepared by methods of the present disclosure was found to be moredifficult to carboxylate than commercially available THCA, providingevidence for a unique polymorph.

Example 2

Methods of the present disclosure generated a crystal polymorph thatappears to he the result of solvent effects caused by the acetonitrile.Melting point of THCA polymorph/salt of the present disclosure is,137-142 degrees C. Stability to decarboxylation of a typical THCA richextract is moderate, while stability of THCA polymorph/salt of thepresent disclosure is resistant.

Process for Producing Protoshatter using TWS THCA salt/polymorph:Advantages of the present disclosure over Standard Shatter Processinclude: (1) Formulated from purified, discrete feedstocks (bottom-up);(2) Standard shatter depends on quality of plant material andcharacteristics (top-down); (3) Control over flavor characteristics; (4)Standard shatter is limited by plant material only; (5) Formulated withpurified THC and terpene blends to create amorphous, glass state; (6)Standard shatter process is limited by characteristics of the plant; (7)Does not require gaseous, hydrocarbon extraction step; (8) Enablesscale-up and potentially continuous process automation; (9) Standardshatter is limited to batch-wise production and small batch sizes.

Protoshatter Formulas (“a.” is the preferred formula); Preferred Ratioof Ingredients (ideal mass ratio); THC & Terpenes Formula;THCA:THC:Terpenes 11:2:1.5; Plus Phytol Formula; THCA: THC:Terpenes:Phytol 11:1:1.5:0.5.

Preferred Range of Ingredients (weight % range); THC & Terpenes Formula;THCA=70-80%; THC=10-15%; Terpenes=5-10%; Plus Phytol Formula;THCA=70-80%; THC=5-8%; Terpenes=5-10%; Phytol=2-4%.

Protoshatter Laboratory Procedures

Protoshatter has nearly identical physical qualities to a high-valueconcentrate product called shatter. It is a transparent glass, oftenlightly colored with yellow, amber, or red tones. Its consistency rangesfrom brittle to taffy-like. Protoshatter is made by combination of highpurity THCA powder (85-100% THCA by mass, HPLC), raw cannabis distillate(75%-90% THC by mass, HPLC) and terpenes (typically 4-10%). Typical acidpurity used is 93% THCA and greater. It is conceivable that acid as lowas 70% might be used without addition of raw distillate. Typicaldistillate purity is 85% THC. We do have evidence that distillate purityimpacts the formulation process or the consistency of the final product.

The remainder of the mass fraction in THCA powder and distillate islargely other cannabinoids. Most simply, the constituents are mixed andmelted together to yield the product.

Raw distillate is incorporated into the product to facilitateformulation, control consistency and improve shelf-stability. Theproduct ranges in consistency from a brittle glass to a semi-liquid,taffy-like state. We have found that this quality is a function of thefraction of acidic cannabinoid components (predominantly THCA), wherethe addition of raw distillate or terpenes results in a decreasinglybrittle product. The addition of distillate lowers the apparent meltingpoint of the product, allowing for more facile manipulations andformulation.

Shelf-stability is worsened by high purity of acid or truly crystallineTHCA starting materials. Products made with these inputs are prone to‘sugaring’—a crystallization process forming a form of ‘sugar wax’ orprotosugar—during either formulation (spontaneous, on heating) or onstanding over time. While typically undesired during protoshatterformulation, sugar is also a very high value product and methods for itsproduction should be protected as well.

This crystallization process requires a measure of liquidity to theproduct, so very brittle products may require heating to sugar and notprone to sugaring at room temperature. Despite a lower purity, productstrending towards a liquid state are also prone to sugar, especially asterpenes evaporate.

As a result, methods for the formulation of protoshatter differdepending on the purity and polymorphism of the input THCA material.THCA powder crystallized from acetonitrile (MeCN) requires greatertemperatures to formulate to protoshatter, and is prone to sugaringduring this process. Amorphous, non-crystalline THCA powder requiresless heating to formulate and mixes more easily with terpenes.

The following are some example experimentals for the formulation ofprotoshatter by different means.

Formulation from Amorphous THCA Powder

Mortar and Pestle Method. To a mortar and pestle is added 2.00 gdecolorized THCA powder. Targeting a sample that is 7% terpenes by mass,to the pile of powder is added 151 mg (approx. 178 microliters) ofTropical Trainwreck terpene blend dropwise. The components are lightlymixed with a spatula, then compounded together with the mortar andpestle yielding a relatively hard, sticky paste.

The contents of the mortar and any product adhering to the pestle arescraped onto a 16.times.24″ sheet of parchment paper. The parchmentpaper is folded in half, to contain the product within it as an‘envelope.’

The product, contained within parchment paper, is then melted by heatingon a hotplate preheated to 140-200 C for 2-10 seconds, or until itbegins to melt. The parchment is quickly flipped and the product isheated again for the same period until the product is completely melted.The parchment containing the melted product is quickly set on a hard,flat surface and the product is rolled flat between the parchment paperusing a rolling pin or other cylindrical roller, to form a thin sheet ofproduct. Once rolled flat, the product is allowed to cool to roomtemperature and solidity.

In flatness embodiments, the product that needs to be flattened, can beflattened with a rolling pin, with clamp press, and so on, can have thefollowing thicknesses. The thickness can be that measured at theapproximate center of the flattened product, or the thickness can be theaverage of the thickness measured at twelve different equally spacedpositions on the flattened product.

Whatever the method used for measuring thickness, the thickness can be0.2 mm, 0.4 mm, 0.6 mm, 0.8 mm, 1 mm, 2 mm, 4 mm, 6 mm, 8 mm, 10 mm (1cm), 1.5 cm, 2.0 cm, 2.5 cm, 3.0 cm, 3.5 cm, 4.0 cm, 4.5 cm, 5 cm, 6 cm,7 cm, 8 cm, 9 cm, 10 cm, 15 cm, 20 cm, 30 cm, 40 cm, and so on. Also,the thickness can be about 0.2 mm, about 0.4 mm, about 0.6 mm, about 0.8mm, about 1 mm, about 2 mm, about 4 mm, about 6 mm, about 8 mm, about 10mm (about 1 cm) about 1.5 cm, about 2.0 cm, about 2.5 cm, about 3.0 cm,about 3.5 cm, about 4.0 cm, about 4.5 cm, about 5 cm, about 6 cm, about7 cm, about 8 cm, about 9 cm, about 10 cm, about 15 cm, about 20 cm,about 30 cm, about 40 cm, and so on. In other thickness embodiments, thethickness can take the form of a range between any two or more adjacentnumbers, that is, in the above lists of numbers.

The sheets of parchment are carefully opened to reveal the thin sheet ofproduct, adherent to one side of the parchment envelope. The semi-solidproduct is then pooled by folding the product over onto itself causingit to cohere, then carefully separating the product from one of the twosheets of parchment.

After repeated folding, the product is now a much thicker ‘slab.’ Asabove, this slab is again placed between the opposing sheets of a sheetof parchment folded in half. The slab is again melted on a hot plate orgriddle until made liquid, then again rolled flat into a large sheet,and allowed to cool to room temperature.

The product is again pooled into a thicker slab, and the process isrepeated once more for a total of three melting, rolling and mixingrepetitions.

After the third mixing event, the sheet of protoshatter may be transerred to storage or packaging for sale. At this stage, the photoshattercan be briefly warmed with a heat:gun, causing it to melt—or“puddle”—into a visually appealing, transparent, glassy product.

DAC Method. To a 50 mL (75 #) DAC cup is added 13.9 grams decolorizedTHCA powder. To make a product loaded at 6% terpenes, 1.04 mL Berry GDP(880 mg) terpene blend is added dropwise. The cup is capped tightly andallowed to cool to −30 C in a freezer.

After 30 minutes of cooling, the contents of the cup are mixed in theDAC mixer (80 s, 2750 rpm) resulting in formation of a red, hard paste.

The paste is scraped from the DAC cup onto a sheet of parchment paper.The paper is folded in half to contain the product. The packet is thenmelted on a hotplate heated to 140-200 C for 2-10 seconds a side, thentransferred to a hard flat surface and rolled into a flat sheet betweenthe two pieces of parchment using a rolling pin. After cooling to roomtemperature and hardening, the parchment envelope is carefully openedand the product formed into a thicker slab by repeated folding uponitself. The melting, rolling process is repeated to ensure homogeneity.Upon cooling, the product is removed from parchment paper and heated forthree seconds it a heat gun, causing it to form a transparent glassyproduct. Yield is 14 g protoshatter.

Formulation from Crystalline THCA Powder

Solution-Phase Pre-formulation. Pre-formulation is used to makeamorphous THCA powder from crystalline THCA powder and to dilute it withraw. This enables manual formulation using the methods above (Mortar andPestle Method).

To a 500 mL 2-neck round bottom flask outfitted with funnel and overheadstirrer is added 38.9 raw distillate followed by 150 mL n-pentane. Thecontents of the flask are stirred to dissolve the distillate(approximately 30 minutes). To a 2 liter, 3-neck flask outfitted withoverhead stirrer, septum and funnel is charged 111.0 grams crystallineTHCA powder. 400 mL pentane is added and the flask stirred. Aftercomplete dissolution of the distillate, the pentane solution istransferred to the 2-liter flask. The 500 mL flask is washed with 150 mLadditional pentane and this rinse is also transferred to the 2-literflask. The flask is stirred to achieve complete dissolution of allcontents (approximately 1 hour).

After 1 hour, the resulting THCA/distillate pentane solution is dividedinto two fractions (by mass) which are charged to two separate 3-literround bottom flasks. Solvent is removed from both flasks by rotaryevaporation yielding a voluminous, foamy off-white solid. The flask istransferred to a vacuum manifold and purged on high vacuum for 48 h toremove solvent.

Once the flasks have reached a constant mass (48 h), they are removedfrom high vacuum and scraped with laboratory spatulas to yield 246.5 gslightly off-white powder. The powder is stored under nitrogen.Following pre-formulation, the product is formulated into protoshatterusing methods for amorphous THCA powder (Mortar and Pestle Method).

Solid Phase Pre-formulation and Syringe Pump Method. To a 50 mL DAC cup(75 #) is added 14.3 g crystalline THCA powder, 2.4 g raw distillateadded. The cup is chilled to −30 C in a freezer (30 minutes). The cup isthen submitted to mixing in the DAC speed mixer (40 seconds, 2750 rpm)yielding an off-white powder with small chunks. This freezing/mixingsequence is repeated until a homogeneous, fluffy, off-white powder isachieved. Yield of pre-formulated powder is 16.7 grams. Typically, atotal of 2-3 mixing cycles are sufficient.

To the DAC cup as above, containing 16.7 g powder is added 1.48 mL (1.26grams) Pineapple Super Silver Haze terpene blend to yield a 7%dispersion. 7.0 grams of this dispersion—a paste—is manually loaded intoa 10 mL gas-tight glass syringe with 14G, 2″ needle. The barrel of thesyringe is wrapped with heat tape. The needle is wrapped with heat tapeor threaded through a heated stainless steel bar with small bore.

The barrel of the syringe is heated to 50-80 C and the needle heated to100-200 C. The exact parameters ideal for final formulation ofprotoshatter arc somewhat indeterminate and seem to vary depending on avariety of factors. The syringe barrel is heated to prewarm the pasteand to lubricate the syringe. 55-60 C is ideal. The temperature of theneedle directly affects the product form. At temperatures lower thanideal, a cloudy, paste-like product is produced.

The syringe pump is set to 0.5-2.0 mL/min and a sheet of parchment paperpositioned under the needle outlet. The pump is activated, extrudingprotoshatter in long strings. After dispensing the whole syringe, theproduct on parchment is briefly warmed on a hotplate then pooled byfolding over repeatedly. The slab of product is briefly heated with aheat gun on its surface to yield 6.7 grams protoshatter as a transparentamber glass.

The present invention is not to be limited by compositions, reagents,methods, diagnostics, laboratory data, and the like, of the presentdisclosure. Also, the present invention is not be limited by anypreferred embodiments that are disclosed herein.

What is claimed is:
 1. A method of purifying cannabinoid acids,comprising: (a) preparing a plant extract comprising cannabinoid acids,(b) isolating the cannabinoid acids from the plant extract in thepresence of a base consisting of lithium carbonate using an extractionprocess.
 2. The method of claim 1, wherein the plant extract is cannabisor hemp plant extract.
 3. The method of claim 1, further comprisingcrystallizing one or more of the isolated cannabinoid acids.
 4. Themethod of claim 3 wherein the isolated cannabinoid acids are inamorphous form.